The cyclic nucleotides are a class of neuroeffectors which appear to play an important role in various types of cellular interactions. A number of experimental models have been used to examine the relationship between the cyclic nucleotides and CNS excitability in vivo. Cyclic nucleotide levels were measured in the cerebellum and the cerebral cortex of the following groups: 1) anoxic animals, 2) seizing animals, both chemically and electrically induced, 3) mice treated with anticonvulsants, 4) anesthetized mice, 5) hibernating hamsters and 6) wobbler mice. Cyclic AMP levels increased in both regions during anoxia and seizures exhibiting tonic extension. Cyclic AMP was not pharmacologically responsive. Generally, cerebellar cyclic GMP was lower after anticonvulsants and CNS depressants and elevated following convulsants and CNS stimulants. Cyclic GMP in the cerebral cortex was paradoxically elevated during halothane anesthesia and after convulsants. Cyclic GMP decreased in both regions during either hibernation or an anoxic insult.